The amygdaloid complex has long been implicated in the organization of visceral, endocrine and autonomic aspects of species-specific behavior, and such affective responses as aggression and defense, sexual arousal, and appetitive behavior. More recently, however, neuropsychological studies of the primate amygdala have clearly shown that it also has a role in cognitive functions such as associative memory. These newly uncovered roles for the primate amygdala are consistent with its widespread connections with the cerebral cortex. While there is little evidence of direct projections between the amygdala and the neocortex in non-primates, in the monkey brain, it has recently been found to project to much of the frontal, temporal, insular and occipital cortices including primary sensory, unimodal associational, and polymodal associational areas. Most of these amygdalocortical projections have only just been identified and the analysis of their anatomical organization is at a very early stage. The goals of the proposed studies are: first, to determine the topographic organization of the amygdalocortical projections with special reference to regional and cross modality divergence; and second, to determine candidate neurotransmitters for these projections. Specifically, the topography of the amygdalocortical projections will be studied by injecting fluorescent dyes with distinct emission spectra into different cortical regions and analyzing sections through the amygdaloid complex for single and/or double retrogradely labeled cells. Neurotransmitter candidates will be examined by two different strategies. In the first, the possibility that these connections are mediated by an excitatory amino acid will be studied by injecting D-3H-aspartate into cortical terminal fields and examining the amygdaloid complex for retrogradely labeled cells. In the second strategy, the distribution of neurons containing other putative neurotransmitters will be studied immunohistochemically using antisera directed against a variety of peptides, such as somatostatin, and specific enzymatic markers, such as glutamic acid decarboxylase. Lesions of the human amygdaloid complex have been found to result in a variety of behavioral and cognitive disturbances. For example, such damage has been linked to the development of temporal lobe epilepsy. It is also known that the amygdala is one of the first structures to demonstrate histologic changes in Alzheimer's disease. The anatomical organization of the amygdala also appears to be abnormal in childhood autism. Moreover, the fact that the amygdala has one of the highest brain levels of benzodiazepine receptors is suggestive that it may mediate the antianxiety effects of these drugs. Knowledge of the amygdalocortical interconnections will advance our understanding of the normal and pathological functioning of this prominent component of the limbic system.